Nutritional composition containing methionine

ABSTRACT

An enteral food composition for clinical or dietary use, comprises, in addition to carbohydrates and proteins or their hydrolysates the following components or their nutritional equivalents, per daily dosage: methionine (0.6-7 g), cysteine (0.5-2.5 g), folic acid (0.4-8 mg), pyridoxal (vitamin B 6) (3-20 mg), zinc (18-120 mg) and at least 400 kcal energy in the form of carbohydrates. These amounts are well above the Recommended Daily Allowance (RDA) values. Further preferred components include lecithin, cyanocobalamine, betaine and magnesium, as well as transsulfuration metabolites, ATP enhancers and antioxidants.

FIELD OF THE INVENTION

[0001] The present invention relates to a module of nutritionalcomponents which supports total methionine metabolism in man, for use ina universal medicinal food. The invention also relates to food productscontaining this module and to a method of producing food products byusing selected amounts of the module.

BACKGROUND

[0002] Methionine is metabolised in man via a multi-step pathway, thetranssulfuration pathway. Several intermediate products are formed inthis pathway, which play a dominant role in other biochemical pathwaysas well. For example, the reaction product S-adenosyl methionine isextensively used in many methylation reactions; homocysteine is the mainmethyl acceptor in folate metabolism and also the conversion of betaineto dimethylglycine (via methylation of homocysteine) strongly influencesfolate metabolism.

[0003] Another intermediate in the transsulfuration pathway iscystathionine generated by reaction between homocysteine and serine,that may split into cysteine and 2-oxy-butyrate. The latter is involvedin the metabolism of several other compounds (e.g. threonine). Cysteineis metabolised to various useful products such as taurine and sulphates.It is also an important precursor for glutathione in the liver and someother tissues. Glutathione that is produced in the liver has to betransported to cell compartments in some peripheral organs in order toexhibit its activity. Intracellular glutathione levels are in turnstrongly influenced by the presence of reducing equivalents and aminoacids in the cell.

[0004] Herein we define total methionine metabolism as those biochemicalpathways which occur in mammals and in which metabolites of themethionine transsulfuration pathway (methionine, S-adenosyl methionine,S-adenosyl homocysteine, homocysteine, cystathionine and cysteine) andmain metabolites thereof (taurine and glutathione) are involved (seescheme below).

[0005] Many diseases in man have been associated with impairedfunctioning of parts of total methionine metabolism. Lack of the bodycapacity for methylation (by shortages of available S-adenosylmethionine) has been related to diseases like cancer, improper woundhealing, diabetes, neurological diseases like Alzheimer or Parkinson'disease (WO 96/33703). Shortages of folate have been associated withneural defects and several other problems.

[0006] Dysfunction of methionine metabolism may also lead to increasedhomocysteine plasma levels, which are associated with cardiovascularproblems. Cysteine deficiencies may lead to low taurine levels, lowsulphation capacity and low intracellular glutathione levels. Shortagesof cysteine have been associated with diseases like diabetes,cardiovascular disease, cancer, rheumatoid arthritis, etc.

[0007] Glutathione can play many important roles in the cell. Asubstantial part of glutathione must be in the reduced form (having aspecific redox potential) in order to allow it to be active.Deficiencies of glutathione have been associated with all kinds ofradical-mediated diseases, such as chronic inflammations, rheumatoidarthritis, with the occurrence of cancer and impaired immune functionsagainst infection.

[0008] EP-A-532369 (Bissbort) describes the pharmaceutical use ofL-methionine for enhancing the methylation capacity in man, e.g. forimproving the immune response, combating viral infections and increasingcreatine production. Methionine may be combined with folic acid,pyridoxine (vitamin B₆), cyanocobalamine (vitamin B₁₂) and magnesium. Adaily dose comprises 1.5-5 g (3 g) of L-methionine, 250-2500 mg (600 mg)of magnesium chloride, 30-120 mg (100 mg) of magnesium carbonate, 0.6-20mg (8 mg) of folic acid, 1.5-25 mg (10 mg) of vitamin B₆ and 15-25 μg(20 μg) of vitamin B₁₂.

[0009] WO 93/15738 (Waldthaler) discloses medicaments containing thymineor its equivalents in combination with methionine, pyridoxine and/orcyanocobalamine and optionally penicillin G for the treatment ofdisorders in the folate metabolism.

[0010] WO 96/02252 and WO 96/33727 (Knoll) disclose the use ofS-adenosyl-L-methionine for the treatment of damage caused by temporaryand permanent local ischaemias, respectively.

[0011] EP-A-347864 (Strydom) discloses an anti-atherogenic agent whichlowers the plasma level of free sulphydryl groups of homocysteine andcysteine and which can contain oxidising agents and folic acid,pyridoxine (vitamin B₆), cyanocobalamine (vitamin B₁₂) and choline orbetaine.

[0012] Likewise, EP-A-595005 and EP-A-595006 (Vesta) teach the use, foradults and infants respectively, of specific ratios of folic acid,pyridoxine and cyanocobalamine for suppressing high homocysteine andmethionine levels in plasma, which are the cause of metabolicdisturbances. According to the latter document, pyridoxine should atleast partly be present in its accessible pyridoxal form. Riboflavin(vitamin B₂), ascorbic acid (vitamin C), tocopherol (vitamin E), zincand selenium may also be present.

[0013] EP-A-705542 discloses a complete dietary composition foradolescents and especially for children of 1 to 6 years having diseasessuch as intestinal disorders. The composition contains 50-65 (63) energy% of carbohydrates, 20-35 (25) en. % of fats and 10-20 (12) en. % offree amino acids with a specific amino acid content.

[0014] A multivitamin preparation supporting the immune system isdisclosed in GB-A-2,292,522. It contains an amino acid blend, vitaminsC, E, A, D and B complex, minerals and trace elements. Important aminoacids are: methionine (90 mg), valine, leucine, threonine (70 mg),phenylalanine, lysine, isoleucine and tryptophane. Levels of B complexvitamins may be: B1 (50 mg), B2 (100 mg), B6 (100 mg), pantothenic acid(300 mg), nicotinamide (50 mg), B12 (2.5 μg), folic acid (150 μg) andbiotin (50 μg). The preparation does not contain carbohydrates or fullproteins. No recommended dosages are given.

[0015] U.S. Pat. No. 5,215,750 discloses a composition for inducingweight loss, containing glutamine as the major component, and further abroad range of vitamins and minerals, without further amino acids,proteins, carbohydrates or fats.

[0016] Despite these proposals, the diseases referred to above are stillvery common and therefore there exists a need for nutritional productsthat may support prevention and treatment of these diseases.

[0017] Many persons suffer from deficiencies in essential amino acids,such as methionine, essential fatty acids, vitamins, minerals, traceelements or other food components, as a result of bad eating habits,disorders in nutrient absorption, or increased nutrient demands. Aminority of patients suffer from metabolic disorders in thetranssulfuration pathway; some enzymes have low activity or do notfunction at all. Thus there is a need for a nutritional product whichsupports total methionine metabolism and at the same time compensatesfor the shortages in nutrients that may occur in patients in need ofsupport of methionine metabolism.

[0018] Several intermediates of total methionine metabolism can be quitereactive in the human body, and the reactive forms (reducedhomocysteine, cysteine, glutathione) are not easily transported over thecell membranes. It is therefore important to support the methioninemetabolism in such a way that no undesired side effects occur and at thesame time intracellular levels of useful intermediates are maintained,even in the diseased state.

[0019] The reactive species are also easily oxidised in aqueoussolution, and it is therefore an object of the invention to provide anutritional composition with a sufficient shelf stability. Somenutritional components that play an important part in the methioninemetabolism have bad organoleptic properties. It is therefore an objectof the invention to provide a nutritional product that is wellacceptable to the consumer.

[0020] Many attempts have been made up to now to find solutions to theseproblems. All these prior attempts have concentrated on a part of thetotal methionine metabolism, relying on an adequate functioning of therest of the biochemical pathways of total methionine metabolism in manto maintain homeostasis and meet physiological demands. For supportingthese parts, either too low or too high amounts were suggested.

[0021] It has now been found that it is essential to provide patientswith a combination of components that play a key role in the variousparts of total methionine metabolism as depicted in the scheme below,and to provide them in an excess amount in the form of a (medicated)nutritional composition in order to give nutritional support to themaximum number of patients. In this context “nutritional” means at leastpartly satisfying the energy needs in addition to having a medicinaleffect.

[0022] It has furthermore been found to be advantageous to administerother components that play a role in total methionine metabolism aswell. Such other components comprise end products and intermediates forgiving a more rapid response and for meeting requirements for thosepatients that have deficiencies in one or more key enzymes that areinvolved in total methionine metabolism.

[0023] The invention pertains to an enteral food composition containingat least digestible, in particular glucose or α-glucan, carbohydratesand proteins or protein hydrolysates and a combination of activecomponents as defined in the appending claims. The amounts of thecomponents of the food composition of the invention are related to theRecommended Daily Allowance (RDA) and other recommendations as used instandard nutrition literature. The reference values based on these RDAvalues for components that can be used according to the invention,together with the preferred ranges of total intake per day, are given intable 1 below. The reference are based on healthy adults having a bodyweight of 70 kg. For patients of different condition and different bodyweight, the levels should be adapted accordingly. It is to be understoodthat on average the energy intake per day should be about 2000 kcal.

[0024] Where reference is made to nutritional equivalents of thecomponents, this includes any compound which under physiologicalconditions yields the component in question in equimolar amounts. TABLE1 Reference values and preferred levels according to the inventionreference general preferred component mg/day mg/day mg/daymethionine/cysteine* 1100   600-7,000 1,600-4,000 folic acid 0.2 0.4-8  0.6-3   pyridoxal 2.0 3.2-20   4-12 cyanocobalamine   0.0015 0.002-0.02 0.0036-0.01  magnesium 300 200-700 300-500 riboflavin 1.5  2-10 2.5-6  niacin 17 NE  25-170 35-85 thiamine 1.5  2-10 3-6 zinc  12  24-120 24-100 manganese  6  9-60 10-30 copper 2.0  3-14  4-10 selenium  0.070.08-0.3   0.1-0.15 ascorbic acid  65 100-900 150-300 tocopherol 10 a-TE 15-180 20-40

[0025] Nutritional equivalents of amino acids include di- oroligopeptides incorporating said amino acid, esters, amides and salts ofthe amino acids, as well as S-substituted derivatives in the case ofsulphur-containing amino acids, including methionine,S-acetylmethionine, S-acetylhomocysteine, homocysteine, cystathionine,cysteine, cystine, glutathione and other dimers and trimers derived fromthese. The sulphur amino acids other than methionine and cysteine can beused instead as a substitute of methionine and cysteine, although thelatter two are preferred. Suitable examples of a cysteine equivalent areN-acetylcysteine and bisglycylcystine. Proteins may also be used asamino acid sources, provided that the desired amino acids become readilyavailable by digestion. Methionine-rich proteins include e.g. casein,caseinates and casein hydrolysates. Cysteine-rich proteins include dairywhey proteins and specific proteins thereof such as lactalbumin, as wellas blood proteins, egg proteins and other proteins which are rich insulphur-containing amino acids and hydrolysates thereof. Thus therequired level of sulphur-containing amino acids can be attained e.g. bycombining casein with cysteine, N-acetylcysteine or a cysteine-richpeptide or by combining whey protein with methionine or amethionine-rich peptide. Preferably, proteins that are rich in essentialamino acids are also present.

[0026] Nutritional equivalents of pyridoxal (vitamin B₆) includepyridoxal phosphate, pyridoxine and pyridoxamine and salts and the like.Nutritional equivalents of niacin (nicotinic acid) include niacinamide(nicotinamide) and tryptophan. The preferred equivalent of thiamine(vitamin B₁) is its hydrochloride.

[0027] Among the components given in table 1, methionine/cysteine, folicacid, pyridoxal and zinc should be present in addition to the energycontent. These components, including the carbohydrate content, werefound to be essential as primary support of the transsulfurationpathway. At least half of the methionine/cysteine content should consistof methionine or a methionine equivalent. A second group of importantcomponents includes magnesium, cyanocobalamine and betaine/choline.Preferably, at least one of these is also present in the foodcompositions of the invention. Magnesium is preferred, but at around orslightly above the reference level only. Suitable magnesium saltsinclude magnesium hydrogen phosphate and magnesium sulphate. A thirdgroup comprises transsulfuration products, including creatine,carnitine, taurine and nucleotides. At least one of these is alsoadvantageously present in the food composition. A fourth group ofcomponents is important as they stimulate carbohydrate metabolism andproduce ATP and reducing equivalents. At least one member of this groupwhich includes pyruvate, thiamine, riboflavin, niacin, biotin andthioctic acid, is preferably present as well. A final group comprisesascorbic acid, tocopherol, selenium, copper and manganese. Theincorporation of ascorbic acid and/or tocopherols is preferred forensuring that reduced glutathione is spared from excessive attack byradicals or oxidation processes. Ascorbic acid may be present as anutritionally acceptable salt, and tocopherol as any one or acombination of isomers, e.g. tocopherol. Other antioxidants or radicalscavengers like carotenoids, flavonoids, uric acid etc. may be includedas well. Similarly, the trace elements Cu, Se and Mn are preferablyincluded, as they are essential for key enzymes that neutraliseoxygen-containing radicals. The preferred range for Cu and Mn is 2-5times the reference value; for selenium it is about 1.5 times thereference value.

[0028] The other components of table 1 are also preferred individually,i.e. the selection of a single component, e.g. riboflavin or manganese,forms a distinct embodiment of the invention. Components for which areference level is not given in table 1, are also advantageouslyincorporated in the composition of the invention. The methyl donorbetaine (N,N,N-trimethylglycine, as its inner salt or its hydrochloride)and/or one of its precursors choline and phosphatidylcholines (occurringin certain lecithins) is preferably included in order to stimulate anindependent pathway for the conversion of homocysteine to methionine.For reasons of taste, betaine itself is preferred over its equivalents.

[0029] Creatine (N-guanidyl-N-methylglycine) can be incorporated assuch, as its phosphate or as an analogue such as guanidine derivatives,in the levels indicated, with a preferred level of around 10 g/day.L-Carnitine can be given as such (inner salt) or as its hydrochloride.Creatine and/or carnitine are especially preferred for patients having apoor blood circulation, or suffering from local ischaemic conditions.D-Biotin (generally preferred) and taurine can be included as such,taurine especially for infants and neurological patients. Nucleotidescan also be advantageously included, preferably as yeast extract in anamount of about 0.1-4 g/day, for example in products for the treatmentof inflammatory diseases of the gut.

[0030] Pyruvate is another component that can contribute to the ATPproduction and can protect glutathione as a radical scavenger. Thepreferred level is from 2 to 20 g/day, especially 4-8 g/day. Pyruvatecan be incorporated e.g. as free acid or as its Ca, Na or K salt.DL-Thioctic acid (lipoic acid) is also preferred for increasing thelevel of ATP produced. Niacin, riboflavin and thiamine also stimulatecarbohydrate metabolism and produce ATP and reducing equivalents.

[0031] Furthermore, usual components can be incorporated at or above therecommended amounts, especiallycalciferol/cholecalciferol/dihydrocalciferol (vitamin D) and phosphate.The composition should comprise sufficient levels of essential aminoacids such as lysine in accessible form, so that the total intakecorresponds at least to the reference levels. Some non-essential aminoacids are also preferably included in the composition of the invention.These comprise especially serine, and furthermore glutamine andarginine/ornithine at the indicated levels as such (L-form) or as easilydegradable peptides or proteins. Threonine is preferably not present inimportant amounts, i.e. preferably lower than 5.2 g per 6.25 g ofnitrogen (<5.2 g per 100 g of proteinaceous material). Proteins whichare low in threonine include acid whey.

[0032] The compositions contain carbohydrates, preferably proteins andpreferably fats. In a complete food, the carbohydrates should constituteat least 25% of the required energy content, i.e. at least 400 kcal/day,up to 1500 kcal/day. The carbohydrates can comprise mono-, di-, oligo-and polysaccharides, such as glucose, fructose, maltose, sucrose,fructo-, galacto- and especially gluco-oligosaccharides, starch, starchhydrolysates and starch fractions and the like. The carbohydratecomposition can be adapted to the type of patients. For diabetespatients, slowly degrading carbohydrates like fructose polymers may bepresent together with a relatively large amount of high molecular weightmaltodextrins. Generally, the carbohydrate compositions is low inlactose. The compositions may furthermore contain dietary fibres such anon-digestible carbohydrates. The proteins may be those described aboveas sources for the desired amino acids, including milk proteins, eggproteins, blood proteins. For reasons of taste, it is preferred that atleast half of the total proteinaceous material (proteins, hydrolysatesand amino acids) is in the form of proteins or peptides, especially inthe form of intact proteins.

[0033] The fats may comprise normal fats C₁₂-C₁₈ derived from saturatedand especially unsaturated fatty acids. The fats may include mediumchain triglycerides derived from C₈ and C₁₀ fatty acids (e.g. accountingfor 5-40 wt. % of the fats), and preferably polyunsaturated long-chain(≧C₁₈) fats (PUFA's) derived from ω-3 fatty acids such aseicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (preferablyat least 3 wt. %, in particular 5-15 wt. % of the fats). The ω-3/ω-6ratio is preferably from 0.3 to 3. For complete foods, the fat contentis preferably more than 30% of the total energy content, especially morethan 35 en. %, up to 45 en. %. The fats should contain phospholipidssuch as lecithin or an equivalent thereof at a level of 1-20 wt. % ofthe fat content, or 0.3-10 en. %, preferably 0.6-5 en. % of thecomposition. The phospholipids can be partly (i.e. the amount above 5wt. % of the fat content) substituted by equivalents such as choline orbetaine.

[0034] The food composition can have the form of a complete food, i.e.all the nutritional needs of the user. As such it will usuallycontaining 1200-2500 kcal per daily dosage, apart from higher or loweramounts in exceptional cases. The daily dosage amounts are given withrespect to a daily energy supply of 2000 kcal, but can be adaptedaccordingly. The complete food can be liquid, wherein the daily dosageis contained in e.g. 2000 ml; more diluted or, especially, moreconcentrated liquids can also be used. The composition can also be insolid form for reconstitution with water. The complete food can be inthe form of multiple dosage units, e.g. from 3 to 10 per day.

[0035] The food composition of the invention can also be a foodsupplement to be used in addition to a non-medicinal food, containingless than 1500 kcal, in particular 400-1000 kcal, per daily dosage. Suchfood supplement preferably also contains at least part of thecarbohydrate and protein supply, so that the need of essential aminoacids and serine is met with the supplement. A very useful supplementcontains the essential components at the levels indicated above(methionine/cysteine, folic acid, vitamin B₆, zinc and optionallymagnesium, vitamin B₁₂, betaine/choline, serine and/or tryptophan with asuitable carrier such as maltodextrin in dry form, e.g. in sachets of 10g. The content of the sachet may be added to regular food or to foodcomponents so as to provide the daily doses according to the invention.

[0036] The invention also relates to a process of producing a foodcomposition, which comprises preparing a premix of at least saidmethionine/cysteine, folic acid, pyridoxal and zinc, optionally with arelatively small amount of maltodextrin or other carbohydrate as acarrier. Further components are then added to said premix, for exampleby subsequent addition of other premixes. The use of premixes maysimplify and/or standardise the preparation of especially adapted foodcompositions directed at specific needs. Also from an economical pointof view, and from the point of view of minimising mistakes duringprocessing, it is therefore advantageous to produce a single premix ofcomponents that can be used in the manufacture of several types ofenteral clinical nutrition.

[0037] As the module of components supports total methionine metabolism,it has universal benefit in many types of clinical nutrition. Theuniversal character of the food composition of the invention obviatesthe need to await the result of some types of clinical analyses ofpatients. The module can be added in response to specific nutritionaldemands. The compositions can be adapted for clinical nutrition, infantformulae, nutrition for persons at risk for specific diseases, enteralnutrition during pregnancy, and dietetic supplements. The foodcompositions can be used for the treatment or prophylaxis of increasedplasma level of homocysteine, cardiovascular diseases, imparted immunefunction, inflammatory diseases, autoimmune diseases such as arthritis,wound healing after surgery, decubitus, cancer, premature ageing,allergic conditions, neural disorders,

EXAMPLE 1

[0038] Three standard mixtures of active components were prepared by drymixing the amounts as indicated in tables 2 and 3 and optionally table4. TABLE 2 Ingredient mixture A for support of total methioninemetabolism amount per 100 kg of premix A maltodextrins 74 kgL-methionine 8 kg N-acetylcysteine 2 kg folic acid 6 g pyridoxine 60 gzinc sulphate 500 g (=200 g Zn) cyanocobalamine on carrier 30 g (=30 mgB12) magnesium phosphate 3 aq. 14 kg (=2 kg Mg)

[0039] TABLE 3 Ingredient mixture B for support of total methioninemetabolism amount per 100 kg of premix B maltodextrins 89 kg betaine 10kg nicotinamide 510 g NE riboflavine 30 g thiamine.HCl 30 g manganesesulphate 4 aq. 320 g (=80 g Mn) cupric sulphate 5 aq. 150 g (=40 g Cu)

[0040] TABLE 4 Ingredient mixture C for support of total methioninemetabolism amount per 200 kg of premix C maltodextrins 40 kg creatine100 kg L-carnitine 12 kg taurine 400 g ascorbic acid 2.0 kgalfa-tocopherol 200 g TE soy lecithin 5 kg L-biotin on a carrier 200 g(=2 g L-biotine) sodium selenate on a carrier 370 g (=1 g Se) L-serine30 kg L-tryptophan 10 kg

EXAMPLE 2

[0041] Complete enteral tube feeding in dry form.

[0042] The ingredients as listed below are dissolved in 2000 l water.Composition of aqueous phase of complete enteral nutrition amount per2000 1 caseinates (50% Na, 50% Ca) 60 kg protein isolate from acid whey40 kg ingredient mixture A 10 kg ingredient mixture B 10 kg ingredientmixture C 20 kg maltodextrins 280 kg L-arginine 6 kg wheat hydrolysate30 kg fibres (inulin/soy: 2/1) 16 kg calcium phosphate 0.6 kg magnesiumphosphate 0.4 kg sodium chloride 0.9 kg potassium citrate 5 kg lecithin4.4 kg standard trace element premix 250 g (which comprises 20 g Fe, 3 gCu, 100 mg Mo, 2 mg F, 20 g Zn, 6 g Mn, 66 mg Cr, 200 mg I, 40 mg Co and10 g Se) standard vitamin premix 20 g (which comprises pantothenic acid8 g, thiamine 2 g, riboflavin 2.2 g, niacin 4.2 g NE, vitamin B6 2.6 g,biotine 200 mg and folic acid 260 mg) meso-inositol 50 g yeast extract 1kg

[0043] After dissolving the ingredients, the aqueous phase is set on pH6.5-8 and stirred until use. In a separate tank the fat blend asexemplified below is prepared by methods known in the art (pumping theappropriate amounts in the tank at elevated temperature (e.g. 50° C.)and the fat-soluble vitamins (A, D2, K and E) are added and the mixturestirred until use). Fat blend composition; amounts in kg per 100 kgsunflower oil (high oleic acid) 28 sunflower oil 12 rapeseed oil 52 fishoil (high DHA) 2 MCT oil 6 vitamin premix vitamin A 1.4 g vitamin D2 10mg vitamin K 100 mg vitamin E 100 g

[0044] The aqueous phase is pumped to a homogeniser arranged before apasteuriser and static mixer. The fat phase is carefully dosed to theaqueous phase before it reaches the mixer, in a ratio of 1 part fatphase to 16 parts of the pasteurised aqueous phase. Immediatelythereafter the mixture is homogenised and pumped to a heat exchangerwhere the water is evaporated and the resulting product spray-dried andpacked in cans.

EXAMPLE 3

[0045] A nutritional supplement for the elderly

[0046] In 2000 liter tap water are dissolved: 70 kg skimmed milk powder(delactosed) 64 kg saccharose  5 kg soy lecithin 10 kg algae oil 10 kgcanola oil

[0047] This mixture is pasteurised and fermented.

[0048] Then are added: 20 kg mixture A (of example 1) 6 kg pectine 200kg glucose syrup (Glucidex) 2 kg choline chloride 2.4 kg calciumchloride 2.4 kg potassium phosphate 1.5 kg potassium lactate 260 gsodium ascorbate 2.0 kg potassium citrate 40 kg fruit concentrate 1 kgflavourings

[0049] The mixture is set on pH 3.8-4.4, pasteurised and filledaseptically into 500 ml cartons.

EXAMPLE 4

[0050] Supplement for persons with volume restrictions (infants, personssuffeying from illness, cancer or neuropathic diseases)

[0051] Packed in 1 liter cartons. Amount per 100 ml Energy 150 kcalProtein (casein/whey 80/20) 8.2 g (=0.3 g Met + Cys) Tryptophan 0.1 gCarbohydrates 16.5 g Maltodextrin 10.5 g Sucrose 6.0 g Fats 5.5 gSaturated 1.3 g Mono-unsaturated 1.8 g PUFA's 2.1 g from vegetable oils,lecithin + DHA/EPA source (0.1 g) Fibre (inulin/soy 1:1) 0.4 g Sodium60-100 mg Potassium 140-210 mg Chloride 80-150 mg Calcium 230 mgPhosphorus 150 mg Magnesium 35 mg Iron 2.0 mg Zinc 6.0 mg Copper 0.6 mgManganese 2.0 mg Fluorine 0.2 mg Molybdene 10 μg Selenium 10 μg Chromium6.6 μg Iodine 20 μg Vitamin A 166 μg RE Vitamin D 2.0 μg α-Tocopherol4.9 mg Vitamin K 8.0 μg Thiamine 0.4 mg Riboflavin 0.4 mg Niacin 6 mg NEPantothenic acid 0.8 mg Vitamin B₆ 1.0 mg Folic acid 100 μg Vitamin B₁₂0.3 μg Biotin 20 μg Vitamin C 13 mg Betaine 20 mg Taurine 4 mg

EXAMPLE 5

[0052] Food supplement

[0053] The mixture of table 2 (example 1) was filled in sachets of 10 geach.

1. Food composition which is a complete enteral food for clinical ordietary use, containing per daily dosage: (a) an energy content of5024-10467 kJ (1200-2500 kcal), supplied by carbohydrates, fats andproteinaceous material, the carbohydrates accounting for at least 25% ofthe energy content and the proteinaceous material being present in anamount of at least 20 g, at least 50% of the proteinaceous materialbeing present as proteins or peptides, and (b) the following componentsor their nutritional equivalent: 0.6-7 g of methionine and cysteinetaken together, 0.4-8 mg of folic acid, 3.2-20 mg of pyridoxal (vitaminB₆) and 24-120 mg of zinc.
 2. Food composition according to claim 1,wherein a least 30 energy % is in the form of fats, further containingat least 70 g of proteinaceous material per daily dosage, at least 50%thereof being in the form of proteins, and at least 1 g of methionineand at least 0.5 g of cysteine per daily dosage, the compositionoptionally being in the form of multiple dosage units.
 3. Foodcomposition which is an enteral food supplement for clinical or dietaryuse to be used in addition to a non-medicinal food, containing per dailydosage, (a) an energy content from 1675 up to less than 6280 kJ (from400 to less than 1500 kcal), supplied by at least carbohydrates andproteinaceous material, soluble digestible carbohydrates being presentin amount of at least 100 g and the proteinaceous material being presentin amount of at least 20 g, at least 50% of the proteinaceous materialbeing present as proteins or peptides, and (b) the following componentsor their nutritional equivalents, 0.6-7 g of methionine and cysteine,0.4-8 mg of folic acid, 3.2-20 mg of pyridoxal (vitamin B₆) and 24-120mg of zinc.
 4. Food composition according to claim 3, containing1675-4187 kJ (400-1000 kcal) per daily dosage.
 5. Food compositionaccording to any one of claims 1-4, wherein at least one of saidcomponents is comprised in the following amounts, per daily dosage;methionine and cysteine (1.6-4-g), methionine according for at leasthalf of said amount, folic acid (0.6-3 mg), pyridoxal (4-12 mg), zinc(30-100 mg), and at least 800 kcal in the form of carbohydrates.
 6. Foodcomposition according to any one of claims 1-5, further containing atleast 0.8 g, preferably 1.6-1.2 g of phospholipids, per daily dosage. 7.Food composition according to any one of claims 1-6, further comprisingat least one of the following components or their nutritionalequivalents, per daily dosage: cyanocobalamine (vitamin B₁₂) (2-20 μg,preferably 3.6-10 μg), magnesium (200-700 mg, preferably 300-500 mg) andbetaine and/or choline (0.3-6, preferably 0.6-3 g); (b) creatine(0.5-40, preferably 2-25 g), carnitine (0.2-4, preferably 0.4-2 g),taurine (15-150, preferably 30-80 mg), and nucleotides (0.1-4,preferably 0.4-2 g); (c) pyruvate (2-20, preferably 4-8 g), riboflavin(vitamin B₂) (2-10 mg, preferably 2.5-6 mg), niacin (25-170 mg,preferably 35-85 mg), thiamine (2-10 mg, preferably 3-6 mg), D-biotin(50-500, preferably 100-300 μg), and thioctic acid (5-200, preferably10-50 mg); (d) manganese (9-60 mg, preferably 10-30 mg), copper (3-14mg, preferably 4-10 mg), selenium (80-300 μg, preferably 100-150 μg),ascorbic acid (vitamin C) (100-900 mg, preferably 150-300 mg), andtocopherol (vitamin E) (15-180 mg, preferably 20-40 mg); (e) serine(3-12 g) and optionally arginine or ornithine (2-10 g), glutamine (5-30g), the composition containing less than 5.2 g of threonine per 100 g ofproteinaceous material; and preferably at least one component from eachof the groups (a-e).
 8. Food composition according to any one of claim1-7, which is in a liquid form having an energy density of at least 4.2kJ, up to 10.5 kJ/ml (1-2.5 kcal/ml).
 9. Food composition according toany one of claims 1-8, which is in a powder form to be reconstitutedwith water.
 10. Process of producing a food composition according to anyone of claims 1-9, which comprises preparing a premix of at least saidmethionine/cysteine, folic acid, pyridoxal and zinc, optionally withcarbohydrate as a carrier.
 11. Use of a composition according to any oneof claim 1-9 for preparing a medicinal composition for the treatment ofprophylaxis of increased plasma level of homocysteine, cardiovasculardiseases, imparted immune function, inflammatory diseases, autoimmunediseases, arthritis, wound healing after surgery, decubitus, cancer,premature ageing, allergic conditions or neural disorders.